DS8201a and Pembrolizumab in Participants With Locally Advanced/Metastatic Breast or Non-Small Cell Lung Cancer

NCT04042701 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: DS8201-A-U1062018-002489-38KEYNOTE-797MK-3475-797
• Study Type: interventional
• Target: 115
• Locations: 4 countries
• Sites: 30

Brief Summary

This two-part study will include a dose escalation part to determine the recommended dose for expansion of DS8201a and pembrolizumab and a dose expansion part to evaluate efficacy, safety, and tolerability of the combination.

Conditions

Breast Cancer; Non-small Cell Lung Carcinoma

Keywords

Human epidermal receptor 2 positive; Human epidermal receptor 2; Non-small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities (DLTs), Part 1

  Maximum Tolerated Dose (MTD) or recommended dose expansion (RDE) of DS-8201a (Part1) are based on the occurrence of DLTs.

  Within two 3-week cycles (6 weeks)

• Objective Response Rate (ORR), Confirmed by Independent Central Review, Part 2

  Within approximately 30 months

Secondary Outcomes (8)

• Treatment-emergent adverse events

  Within approximately 30 months

• Pharmacokinetic Parameter Maximum Serum Concentration (Cmax)

  Cycle 1, Day 1: predose and postdose, Day 8, and Day 15; Cycle 2, Day 1 predose and postdose, and Cycle 3, Day 1 (each cycle is 21 days)

• Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC)

  Cycle 1, Day 1: predose and postdose, Day 8, and Day 15; Cycle 2, Day 1 predose and postdose, and Cycle 3, Day 1 (each cycle is 21 days)

• Duration of Response (DoR)

  Within approximately 30 months

• Disease Control Rate (DCR)

  Within approximately 30 months

Study Arms (5)

Part 1 (Dose Escalation)

EXPERIMENTAL

HER2-positive breast cancer, HER2-low expressing breast cancer, HER2-expressing NSCLC, and HER2-mutant NSCLC participants who received escalating doses of DS8201a (initial dose 3.2 mg/kg Q3W) and pembrolizumab 200 mg.

Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab

HER2-positive breast cancer (Part 2 Dose Expansion)

EXPERIMENTAL

HER2-positive breast cancer participants with prior ado-trastuzumab emtansine (T-DM1) with disease progression and who received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab

HER2-low breast cancer (Part 2 Dose Expansion)

EXPERIMENTAL

HER2 low breast cancer participants with prior failed standard treatments who received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab

HER2-expressing NSCLC (Part 2 Dose Expansion)

EXPERIMENTAL

HER2-expressing NSCLC participants who had not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents and received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab

HER2-mutant NSCLC (Part 2 Dose Expansion)

EXPERIMENTAL

HER2-mutant NSCLC participants who had not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents and received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab

Interventions

Trastuzumab deruxtecan (DS-8201a) DRUG

Part 1: Two dose levels of DS-8201a (3.2 mg/kg Q3W and 5.4 mg/kg Q3W via intravenous (IV) infusion will be administered for the dose escalation part of the study in combination with pembrolizumab. Part 2: Once Part 1 of the study is complete and a RDE for DS-8201a has been established, Part 2 will begin. All participants will receive DS-8201a at the RDE in combination with pembrolizumab.

HER2-expressing NSCLC (Part 2 Dose Expansion); HER2-low breast cancer (Part 2 Dose Expansion); HER2-mutant NSCLC (Part 2 Dose Expansion); HER2-positive breast cancer (Part 2 Dose Expansion)

Pembrolizumab DRUG

All participants will receive pembrolizumab (200 mg Q3W) via intravenous (IV) infusion prior to DS-8201a in Parts 1 and 2 of the study.

Also known as: KEYTRUDA®

HER2-expressing NSCLC (Part 2 Dose Expansion); HER2-low breast cancer (Part 2 Dose Expansion); HER2-mutant NSCLC (Part 2 Dose Expansion); HER2-positive breast cancer (Part 2 Dose Expansion); Part 1 (Dose Escalation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Adults ≥18 years
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1
• Pathologically documented HER2-expressing locally advanced/metastatic breast cancer, and HER2-expressing or HER2-mutant locally advanced/metastatic NSCLC
• Willing to provide a tumor biopsy during screening and during treatment
• Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator
• Adequate cardiac function, as defined by left ventricular ejection fraction (LVEF) ≥50% within 28 days before enrollment.
• Adequate organ function
• Adequate treatment washout period before enrollment
• Pathologically documented, locally advanced/metastatic breast cancer that has centrally determined HER2-positive expression as per American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) Guidelines
• Received prior trastuzumab emtansine (T-DM1) therapy with documented progression
• Pathologically documented, locally advanced/metastatic breast cancer that has centrally determined HER2-low expression (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization \[ISH-\])
• Participants must have exhausted treatments that can confer any clinically meaningful benefit (eg, other therapies such as hormonal therapy for participants who are hormone receptor positive)
• Pathologically documented, locally advanced/metastatic NSCLC that has centrally or locally determined HER2-expression (IHC 1+, 2+, or 3+)
• Participants who have known epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK), BRAF V600E mutation, or ROS1 fusion should have disease progression after treatment with at least one genomically-targeted therapy for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment

You may not qualify if:

• Prior treatment with pembrolizumab or DS-8201a
• Medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before enrollment to rule out MI
• Corrected QT interval (QTc) prolongation to \>470 ms (females) or \>450 ms (males)
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Spinal cord compression or clinically active central nervous system metastases
• Active, known or suspected autoimmune disease
• Condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment
• Prior therapy with an anti-PD-1 or anti-PD-L1 agent
• Prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
• Prior anti-HER2 therapy is not allowed for participants with HER2 low-expressing breast cancer or participants with NSCLC (Cohorts 2, 3, or 4). Prior treatment with pan-HER tyrosine kinase inhibitor is allowed.
• Prior systemic anticancer therapy, including investigational agents within 2 to 6 weeks prior to treatment
• Unresolved toxicities from previous anticancer therapy
• Live vaccine within 30 days prior to the first dose of study drug
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral breast cancer

Sponsors & Collaborators

• Daiichi Sankyo: lead
• AstraZeneca: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (30)

Univ. of Cali. San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Cancer Specialists of North Florida (Cbo)

Jacksonville, Florida, 32256, United States

Location

Moffitt Cancer Center

Tampa, Florida, 32256, United States

Location

Moffit Cancer Center

Tampa, Florida, 33612, United States

Location

Center for Cancer & Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Siteman Cancer Center-Washington University

St Louis, Missouri, 63110, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Hope Cancer Center of East Texas

Tyler, Texas, 75701, United States

Location

Institut Bergonie

Bordeaux, 33000, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94000, France

Location

CHUTimone

Marseille, 13385, France

Location

Institut PAOLI-CALMETTES

Marsielle, 13273, France

Location

CHU de Poitiers

Poitiers, 86000, France

Location

Univ. du Cancer de Toulouse

Toulouse, 31100, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Hospital Teresa Herrera (C.H.U.A.C)

A Coruña, 15006, Spain

Location

Inst. Oncologico Baselga Hospital Quiron

Barcelona, 08023, Spain

Location

Hospital de la Santa Creu i de Sant Pau

Barcelona, 08025, Spain

Location

Hopital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, 35016, Spain

Location

Hospital General Univ. Gregorio Marañon

Madrid, 28009, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Sarah Cannon Research Institute (SCRI)

London, W1G 6AD, United Kingdom

Location

The Christie NHS Fond. Trust

Manchester, M20 4BX, United Kingdom

Location

Royal Marsden Hosptial

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

trastuzumab deruxtecan; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b, open-label, 2-part, multicenter, non-randomized, multiple-dose study

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 2, 2019
• Study Start: February 10, 2020
• Primary Completion: July 21, 2025
• Study Completion (Estimated): March 31, 2027
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

GB (4); US (10); ES (9); FR (7)